Major finding: Obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47) in premenopausal women; a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14); and no effect in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).
Data source: Analysis of pooled data on 80,000 patients enrolled in 70 clinical trials.
Disclosures: The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.
Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.
An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.
But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.
“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.
There was also no apparent effect among women of any age with ER-negative tumors.
The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.
Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.
“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.
Dr. Yu comoderated the briefing, but was not involved in the study.
The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.
Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.
“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.
“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.
Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,
In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.
They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).
A comparison of obese women (BMI, 30 kg/m2 or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.
The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.